(+-)-Mercaptosuccinic acid → H-Glu(OtBu)-Tyr(tBu)-Leu-OBzl

HRID 523356

Reaktionsgleichung

Reaktionsgleichung von HRID 523356
[NH2:1][C@H:2]([C:15]([NH:17][C@H:18]([C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24])[CH2:19][CH:20]([CH3:22])[CH3:21])=[O:16])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:6][CH:5]=1.C1C=CC2N(O)N=NC=2C=1.[NH:43](C(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O)[C@H:44]([C:54](O)=[O:55])[CH2:45][CH2:46][C:47](=[O:53])[O:48][C:49]([CH3:52])([CH3:51])[CH3:50].CCN=C=NCCCN(C)C.Cl.C(O)(=O)C(CC(O)=O)S.C1CCN2C(=NCCC2)CC1.S(O)(C)(=O)=O>[Cl-].[Na+].O.C(Cl)(Cl)Cl>[NH2:43][C@H:44]([C:54]([NH:1][C@H:2]([C:15]([NH:17][C@H:18]([C:23]([O:25][CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)=[O:24])[CH2:19][CH:20]([CH3:22])[CH3:21])=[O:16])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([O:10][C:11]([CH3:13])([CH3:14])[CH3:12])=[CH:8][CH:9]=1)=[O:55])[CH2:45][CH2:46][C:47](=[O:53])[O:48][C:49]([CH3:51])([CH3:52])[CH3:50]

Komponenten

10

Edukt 7

HCID 6268(+-)-Mercaptosuccinic acidHCID 6395Methanesulfonic AcidHCID 757711-HydroxybenzotriazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2724637Fmoc-L-glutamic acid 5-tert-butyl esterHCID 131735567H-Tyr(tBu)-Leu-OBzl

Produkt 1

HCID 131735568H-Glu(OtBu)-Tyr(tBu)-Leu-OBzl

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6212ChloroformLösungsmittel3×HCID 57417360Sodium chloride; waterLösungsmittel

Versuchsvorschrift

To the chloroform solution (20 ml) of H-Tyr(tBu)-Leu-OBzl was added HOBt (41 mg, 0.30 mmol), Fmoc-Glu(OtBu)-OH (468 mg, 1.10 mmol) and EDC.HCl (232 mg, 1.21 mmol) were added under ice-cooling, and the mixture was stirred at room temperature overnight. After completion of the reaction, to this solution were added under ice-cooling thiomalic acid (450 mg, 3.00 mmol) and DBU (1.49 mL, 10.00 mmol), and the mixture was stirred at room temperature for 3 hr. After completion of the reaction, to this solution was added dropwise under ice-cooling a mixture of MsOH (0.23 mL, 3.60 mmol) and chloroform (2.3 mL), chloroform (10 ml) and 20% brine (20 ml) were added to give an organic layer and an aqueous layer. Then, the aforementioned pH=9.0 washing was performed three times. The obtained organic layer was washed three times with 10% aqueous sodium carbonate solution (20 ml) and twice with 20% brine (20 ml) with stirring at room temperature, and the organic layer and the aqueous layer were partitioned. The obtained organic layer was dried over sodium sulfate and filtered to give a chloroform solution (30 ml) of H-Glu(OtBu)-Tyr(tBu)-Leu-OBzl. This chloroform solution was directly used in the next step.

Aufarbeitung

  1. additionwere added under ice-
  2. temperaturecooling
  3. customAfter completion of the reaction
  4. additionto this solution were added under ice-
  5. stirringthe mixture was stirred at room temperature for 3 hr
  6. customAfter completion of the reaction
  7. additionto this solution was added dropwise under ice-
  8. temperaturecooling
  9. additionwere added
  10. customto give an organic layer
  11. washThen, the aforementioned pH=9.0 washing
  12. washThe obtained organic layer was washed three times with 10% aqueous sodium carbonate solution (20 ml)
  13. stirringtwice with 20% brine (20 ml) with stirring at room temperature
  14. customthe organic layer and the aqueous layer were partitioned
  15. dry with materialThe obtained organic layer was dried over sodium sulfate
  16. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-21e16d89153e4b438b9ea37efff374a0
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09334302B2

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